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Cancers
Special Issues
Emerging Therapies in Renal Cell Carcinoma
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Emerging Therapies in Renal Cell Carcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 20600

Special Issue Editors

Dr. Matthew T Campbell

E-Mail Website
Guest Editor
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Interests: clinical trials; novel therapeutics in renal, urothelial, and rare genitourinary cancers; translational research; renal cell carcinoma; bone metastases; locally advanced urothelial cancer; adrenal cortical cancer
Dr. Tian Zhang

E-Mail Website
Guest Editor
Hematology and Oncology Division, Department of Internal Medicine, University of Texas Southwestern (UTSW), Dallas, TX, USA
Interests: clinical trials; translational research; clinical development of novel therapeutics; biomarkers for genitourinary malignancies; data-driven clinical care

Special Issue Information

Dear Colleagues, 

Therapy for renal cell carcinoma has evolved rapidly in the last decade with the development of modern immune-oncology (IO) agents and second-generation tyrosine kinase inhibitors (TKI). Combinations of these agents have emerged as standard of care front line treatment for patients with metastatic clear cell histology.  Adjuvant IO therapy has now emerged as an option for high-risk localized patients after surgery.   The role of cytoreductive nephrectomy has been called into question, but the role of cytoreductive nephrectomy, metastasectomy, ablative techniques, and radiation continue to play important roles in select patients.  Therapeutic options are also advancing for patients with non-clear cell histologies. For the first time patients with the hereditary cancer syndrome, Von Hippel Lindau, have an approved therapeutic option.

We are pleased to invite you to contribute to this special issue focused on the multitude of therapeutic advances in renal cell carcinoma (RCC). The Aim of this Special Issue is to highlight recent advances in the systemic treatment of VHL syndrome, clear cell, and variant histologies.  We plan to explore emerging IO and pathway targets in various histologies of RCC.  We also plan to highlight the current role of cytoreductive nephrectomy and metastasectomy, current and emerging ablative techniques, current and emerging radiation techniques.  

This Special Issue aims is to highlight the following topics:

  • Therapy development in papillary renal cell carcinoma
  • Therapy development in VHL syndrome
  • Therapy development in renal medullary carcinoma
  • The role of interventional radiology in the treatment of kidney cancer, past, present, future
  • The role of radiation in renal cell carcinoma
  • Pros and cons of adjuvant therapy in the treatment of RCC
  • Optimal treatment selection for front line therapy in clear cell RCC
  • Emerging targets in clear cell RCC
  • Emerging targets in non-clear cell RCC
  • Evolution of IO therapy in RCC present and future (i.e cellular therapy, novel targets)
  • The role of surgery in metastatic clear cell RCC

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

Therapeutic and interventional studies in RCC, translational research projects in RCC, basic science studies in RCC.

We look forward to receiving your contributions.

Dr. Matthew T Campbell
Dr. Tian Zhang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (9 papers)

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Editorial

Jump to: Research, Review

6 pages, 215 KiB  
Editorial
Special Issue Editorial: Emerging Therapies in Renal Cell Carcinoma: The Road to a Cure?
by Matthew T. Campbell and Tian Zhang
Cancers 2023, 15(21), 5262; https://doi.org/10.3390/cancers15215262 - 02 Nov 2023
Viewed by 756
Abstract
In the past two decades, therapy development in the treatment of renal cell carcinoma has exploded [...] Full article
(This article belongs to the Special Issue Emerging Therapies in Renal Cell Carcinoma)

Research

Jump to: Editorial, Review

10 pages, 1266 KiB  
Article
Outcomes of Radiofrequency Ablation for Solitary T1a Renal Cell Carcinoma: A 20-Year Tertiary Cancer Center Experience
by Mohamed E. Abdelsalam, Ahmed Awad, Ali Baiomy, David Irwin, Jose A. Karam, Surena F. Matin, Rahul A. Sheth, Peiman Habibollahi, Bruno C. Odisio, Thomas Lu and Kamran Ahrar
Cancers 2023, 15(3), 909; https://doi.org/10.3390/cancers15030909 - 31 Jan 2023
Cited by 3 | Viewed by 1762
Abstract
Background: The aim is to determine the long-term oncologic and survival outcomes of the radiofrequency ablation (RFA) of solitary de novo T1a renal cell carcinoma (RCC). Materials and methods: We retrospectively reviewed our renal ablation registry and included only patients with new solitary, [...] Read more.
Background: The aim is to determine the long-term oncologic and survival outcomes of the radiofrequency ablation (RFA) of solitary de novo T1a renal cell carcinoma (RCC). Materials and methods: We retrospectively reviewed our renal ablation registry and included only patients with new solitary, biopsy-proven T1a RCC (<4 cm) who underwent RFA from January 2001 through December 2020. We collected patient and tumor characteristics. Survival rates were estimated using the Kaplan–Meier method. Results: Of the 243 patients who met our inclusion criteria (160 male and 83 female, median age 68 years), 128 (52.6%) had another primary malignancy other than renal malignancy. Two-hundred forty-three RFA procedures were performed for 243 renal tumors of a median tumor size of 2.5 cm. The median follow-up period was 3.7 years. Most tumors (68.6%) were clear cell RCC. Ten patients (4.1%) experienced Clavien–Dindo Grade III complications. Seven patients(3.1%) developed recurrence at the ablation zone, and 11 (4.5%) developed recurrence elsewhere in the kidney. The 15-year local-recurrence- and disease-free survival were 96.5% and 88.6%, respectively. The 15-year metastasis-free survival and cancer-specific survival were 100%. Conclusions: RFA is a highly effective modality for the management of T1a RCC, with low complication and recurrence rates. Long-term data revealed favorable oncologic and survival outcomes. Full article
(This article belongs to the Special Issue Emerging Therapies in Renal Cell Carcinoma)
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17 pages, 17982 KiB  
Article
Tat-hspb1 Suppresses Clear Cell Renal Cell Carcinoma (ccRCC) Growth via Lysosomal Membrane Permeabilization
by Lin Zhang, Guang-Zhi Jin and Dong Li
Cancers 2022, 14(22), 5710; https://doi.org/10.3390/cancers14225710 - 21 Nov 2022
Cited by 2 | Viewed by 1425
Abstract
Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer, of which the incidence is increasing worldwide with a high mortality rate. Bioactive peptides are considered a significant class of natural medicines. We applied mass spectrometry-based peptidomic analysis to explore the [...] Read more.
Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer, of which the incidence is increasing worldwide with a high mortality rate. Bioactive peptides are considered a significant class of natural medicines. We applied mass spectrometry-based peptidomic analysis to explore the peptide profile of human renal clear cell carcinoma and adjacent normal tissues. A total of 18,031 peptides were identified, of which 105 unique peptides were differentially expressed (44 were up-regulated and 61 were down-regulated in ccRCC tissues). Through bioinformatic analysis, we finally selected one peptide derived from the HSPB1 protein (amino acids 12–35 of the N-terminal region of HSPB1). Next, we fused this peptide to the HIV-Tat, generated a novel peptide named Tat-hspb1, and found that Tat-hspb1 inhibited ccRCC cells’ viability while being less cytotoxic to normal epithelial cells. Furthermore, Tat-hspb1 induced apoptosis and inhibited the proliferation and migration of ccRCC cells. Furthermore, we demonstrated that Tat-hspb1 was predominantly localized in lysosomes after entering the ccRCC cell and induced lysosomal membrane permeabilization (LMP) and the release of cathepsin D from lysosomes. Taken together, Tat-hspb1 has the potential to serve as a new anticancer drug candidate. Full article
(This article belongs to the Special Issue Emerging Therapies in Renal Cell Carcinoma)
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Review

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12 pages, 1135 KiB  
Review
An Update on the Treatment of Papillary Renal Cell Carcinoma
by Neal S. Chawla, Nicolas Sayegh, Sweta Prajapati, Elyse Chan, Sumanta K. Pal and Alexander Chehrazi-Raffle
Cancers 2023, 15(3), 565; https://doi.org/10.3390/cancers15030565 - 17 Jan 2023
Cited by 4 | Viewed by 4710
Abstract
Papillary renal cell carcinoma (pRCC) is the second-most common subtype of kidney cancer following clear cell renal cell carcinoma (ccRCC), representing 15% of kidney cancers. Despite advances in therapy, including combination strategies with targeted therapies and immune checkpoint inhibitors, progress has lagged behind [...] Read more.
Papillary renal cell carcinoma (pRCC) is the second-most common subtype of kidney cancer following clear cell renal cell carcinoma (ccRCC), representing 15% of kidney cancers. Despite advances in therapy, including combination strategies with targeted therapies and immune checkpoint inhibitors, progress has lagged behind that of ccRCC. This is in part due to the heterogenous nature of the various subtypes of pRCC. More recently, investigators have turned efforts towards histology and biology-based trials. In this review, we outline some of the distinct biological characteristics of pRCC and discuss the most impactful clinical trials to date. Finally, we look ahead to several highly anticipated ongoing trials in pRCC. Full article
(This article belongs to the Special Issue Emerging Therapies in Renal Cell Carcinoma)
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15 pages, 313 KiB  
Review
The Continuing Question of Adjuvant Therapy in Clear Cell Renal Cell Carcinoma
by Stephanie A. Berg and Bradley A. McGregor
Cancers 2022, 14(24), 6018; https://doi.org/10.3390/cancers14246018 - 07 Dec 2022
Cited by 2 | Viewed by 2006
Abstract
Treatment advances in kidney cancer continually evolve. The focus of treatment options continues with oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) or intravenous immune checkpoint inhibitors (ICIs). Multiple trials exploring the role of adjuvant treatment after cytoreductive nephrectomy in [...] Read more.
Treatment advances in kidney cancer continually evolve. The focus of treatment options continues with oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) or intravenous immune checkpoint inhibitors (ICIs). Multiple trials exploring the role of adjuvant treatment after cytoreductive nephrectomy in high-risk clear cell renal cell carcinoma are currently ongoing. The discovery of biomarkers may help determine which patients benefit from these treatments, but these are not yet available outside clinical studies. Trials with combination therapies are also ongoing, especially using novel therapies with new mechanisms of action, and will hopefully provide more clues on proper patient and therapy selection in the adjuvant setting. Full article
(This article belongs to the Special Issue Emerging Therapies in Renal Cell Carcinoma)
12 pages, 283 KiB  
Review
Systemic Therapy Development in Von Hippel–Lindau Disease: An Outsized Contribution from an Orphan Disease
by Vivek Narayan and Eric Jonasch
Cancers 2022, 14(21), 5313; https://doi.org/10.3390/cancers14215313 - 28 Oct 2022
Cited by 3 | Viewed by 1330
Abstract
Over the last several decades, an improved understanding of von Hippel–Lindau disease and its underlying biology has informed the successful development of numerous anti-cancer agents, particularly for the treatment of advanced renal cell carcinoma. Most recently, this has culminated in the first regulatory [...] Read more.
Over the last several decades, an improved understanding of von Hippel–Lindau disease and its underlying biology has informed the successful development of numerous anti-cancer agents, particularly for the treatment of advanced renal cell carcinoma. Most recently, this has culminated in the first regulatory approval for a systemic therapy for VHL disease-associated neoplasms. This review will trace the clinical development of systemic therapies for VHL disease and additionally highlight anticipated challenges and opportunities for future VHL systemic therapy. Full article
(This article belongs to the Special Issue Emerging Therapies in Renal Cell Carcinoma)
21 pages, 755 KiB  
Review
Emerging Targets in Clear Cell Renal Cell Carcinoma
by Yu-Wei Chen, Brian I. Rini and Kathryn E. Beckermann
Cancers 2022, 14(19), 4843; https://doi.org/10.3390/cancers14194843 - 04 Oct 2022
Cited by 9 | Viewed by 3228
Abstract
The dual immune checkpoint blockade targeting CTLA-4 and PD-1 (ipilimumab/nivolumab) or the IO combinations targeting PD-1 and anti-VEGF TKIs (pembrolizumab/axitinib, nivolumab/cabozantinib, pembrolizumab/lenvatinib) have demonstrated an overall survival benefit in advanced clear cell renal cell carcinoma (ccRCC). Despite this significant improvement in clinical outcomes [...] Read more.
The dual immune checkpoint blockade targeting CTLA-4 and PD-1 (ipilimumab/nivolumab) or the IO combinations targeting PD-1 and anti-VEGF TKIs (pembrolizumab/axitinib, nivolumab/cabozantinib, pembrolizumab/lenvatinib) have demonstrated an overall survival benefit in advanced clear cell renal cell carcinoma (ccRCC). Despite this significant improvement in clinical outcomes in the frontline setting from IO/IO or the IO/TKI combinations, there is a subset of patients of advanced ccRCC that do not respond to such combinations or will lose the initial efficacy and have disease progression. Therefore, a remarkable unmet need exists to develop new therapeutics to improve outcomes. With an enhanced understanding of ccRCC biology and its interaction with the tumor microenvironment, several new therapies are under development targeting ccRCC metabolism, cytokine-signaling, alternative immune checkpoint proteins, and novel biological pathways. In addition, microbiome products enhancing IO response, antibody–drug conjugates, and targeted radionuclides are also being investigated. This review summarizes selected emerging agents that are under development in ccRCC. Full article
(This article belongs to the Special Issue Emerging Therapies in Renal Cell Carcinoma)
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13 pages, 984 KiB  
Review
The Emerging Role of Radiation Therapy in Renal Cell Carcinoma
by Michael Christensen and Raquibul Hannan
Cancers 2022, 14(19), 4693; https://doi.org/10.3390/cancers14194693 - 27 Sep 2022
Cited by 9 | Viewed by 2621
Abstract
Advancements in radiation delivery technology have made it feasible to treat tumors with ablative radiation doses via stereotactic ablative radiation therapy (SAbR) at locations that were previously not possible. Renal cell cancer (RCC) was initially thought to be radioresistant, even considered toxic, in [...] Read more.
Advancements in radiation delivery technology have made it feasible to treat tumors with ablative radiation doses via stereotactic ablative radiation therapy (SAbR) at locations that were previously not possible. Renal cell cancer (RCC) was initially thought to be radioresistant, even considered toxic, in the era of conventional protracted course radiation. However, SAbR has been demonstrated to be safe and effective in providing local control to both primary and metastatic RCC by using ablative radiation doses. SAbR can be integrated with other local and systemic therapies to provide optimal management of RCC patients. We will discuss the rationale and available evidence for the integration and sequencing of SAbR with local and systemic therapies for RCC. Full article
(This article belongs to the Special Issue Emerging Therapies in Renal Cell Carcinoma)
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24 pages, 334 KiB  
Review
Determining Front-Line Therapeutic Strategy for Metastatic Clear Cell Renal Cell Carcinoma
by Kevin K. Zarrabi, Oladimeji Lanade and Daniel M. Geynisman
Cancers 2022, 14(19), 4607; https://doi.org/10.3390/cancers14194607 - 22 Sep 2022
Cited by 2 | Viewed by 1835
Abstract
The therapeutic landscape for metastatic renal cell carcinoma has rapidly evolved over the years, and we are now in an era of combination therapy strategies employing immune checkpoint blockade and anti-angiogenesis targeted therapy. Since 2018, we have gained regulatory approval for four distinct [...] Read more.
The therapeutic landscape for metastatic renal cell carcinoma has rapidly evolved over the years, and we are now in an era of combination therapy strategies employing immune checkpoint blockade and anti-angiogenesis targeted therapy. Since 2018, we have gained regulatory approval for four distinct combination therapies, all with survival benefits, and with guideline recommendation for use in the front-line setting. As such, treatment selection has become increasingly complex with a myriad of treatment choices but little high-level head-to-head data to guide treatment selection. Heterogeneity in tumor biology further complicates treatment selection as tumors vary in behavior and treatment responsiveness. Ongoing development of biomarkers will certainly assist in this setting, and validation of predictive markers represents an unmet need. In their absence, we highlight features of disease and nuances to datasets from landmark prospective clinical trials to help inform treatment selection. There is growing evidence to support deferring upfront systemic therapy in some patients, with opportunities for active surveillance or metastasis-directed therapy. In others, upfront systemic therapy is warranted and necessitates thoughtful consideration of multiple clinicopathologic parameters to inform optimal patient-centered decision making. Full article
(This article belongs to the Special Issue Emerging Therapies in Renal Cell Carcinoma)
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